Inventiva S.A. announced that following a routine visit during the course of the NATiV3 trial, an adverse event of liver tests was reported in a patient enrolled in the trial. This event has been assessed as a treatment-related Suspected Unexpected Serious Adverse Reaction (?SUSAR?). The study drug was discontinued for that patient and liver tests which are being closely followed at the clinical site are improving and the patient has been without clinical symptoms throughout the period of observation. Additional lab tests and a liver biopsy performed after study drug discontinuation provided results compatible with autoimmune hepatitis. This patient presented at baseline in September 2022 with a histological diagnosis of NASH with stage 2 fibrosis. An earlier diagnostic analysis had raised a suspicion of autoimmune hepatitis dating back to June 2022. The SUSAR was duly reported to all regulatory authorities and reviewed by the DMC in conjunction with other milder cases of elevation of aminotransferases among trial participants. The DMC subsequently recommended that the NATiV3 trial can continue with the following modifications: liver monitoring every 6 weeks for each patient; and amendment to the protocol to exclude newly screened patients diagnosed or with a predisposition to autoimmune liver or thyroid disease. Following review of the data by the DMC, the Company made the decision to voluntarily pause screening and randomization to implement the DMC recommendations. Patients currently enrolled are continuing to receive treatment under the new liver monitoring schedule recommended by the DMC.
The Company is working diligently to make the appropriate amendments to the study protocol and the Informed Consent Form in line with the DMC recommendations and plans to resume screening and randomization in approximately four to six weeks once the operational implementation of the amendment is completed. Inventiva expects that the screening and randomization pause may extend the last patient first visit timeline for NATiV3 trial to the first half of 2024. This SUSAR is the first reported in all clinical trials with lanifibranor. Prior to this voluntary pause, Inventiva was on track to complete screening by the end of the first quarter of 2024 with over 550 patients in screening and 913 patients randomized in the NATiV3 clinical trial, including 731 in the main cohort. The pause in screening and randomization in NATiV3 is not impacting the publication of the topline results of the Phase IIa, LEGEND, evaluating lanifibranor in combination with empagliflozin and is expected for the first quarter of 2024.